JP5376478B2 - 効率的な人工多能性幹細胞の樹立方法 - Google Patents
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US23240209P | 2009-08-07 | 2009-08-07 | |
| US61/232,402 | 2009-08-07 | ||
| US30730610P | 2010-02-23 | 2010-02-23 | |
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Families Citing this family (93)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2659945C (en) | 2005-08-03 | 2014-12-16 | Advanced Cell Technology, Inc. | Improved methods of reprogramming animal somatic cells |
| KR101679082B1 (ko) | 2008-03-17 | 2016-11-23 | 더 스크립스 리서치 인스티튜트 | 유도 만능 줄기 세포 생성을 위한 화학적 및 유전적 조합 접근법 |
| WO2009115295A1 (en) * | 2008-03-17 | 2009-09-24 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) | Vectors and methods for generating vector-free induced pluripotent stem (ips) cells using site-specific recombination |
| JP5340265B2 (ja) | 2008-06-27 | 2013-11-13 | 国立大学法人京都大学 | 効率的な人工多能性幹細胞の樹立方法 |
| EP2307539B1 (en) * | 2008-07-30 | 2014-11-19 | Kyoto University | Method of efficiently establishing induced pluripotent stem cells |
| CN102317442B (zh) | 2008-12-17 | 2014-08-13 | 斯克里普斯研究所 | 干细胞的产生和保持 |
| US8951801B2 (en) | 2009-02-27 | 2015-02-10 | Kyoto University | Method for making IPS cells |
| WO2011016588A1 (en) | 2009-08-07 | 2011-02-10 | Kyoto University | Method of efficiently establishing induced pluripotent stem cells |
| US8993329B2 (en) | 2009-09-24 | 2015-03-31 | Kyoto University | Method of efficiently establishing induced pluripotent stem cells |
| CN113621576A (zh) | 2009-10-16 | 2021-11-09 | 斯克里普斯研究所 | 多能细胞的诱导 |
| JP5898086B2 (ja) | 2009-11-04 | 2016-04-06 | セルラー ダイナミクス インターナショナル， インコーポレイテッド | 化学物質を用いるエピソームリプログラミング |
| EP2536828B1 (en) | 2010-02-16 | 2015-09-09 | Kyoto University | Method of efficiently establishing induced pluripotent stem cells |
| WO2011119942A1 (en) * | 2010-03-25 | 2011-09-29 | Vistagen Therapeutics, Inc. | Induction of ips cells using transient episomal vectors |
| JP5909482B2 (ja) | 2010-03-31 | 2016-04-26 | ザ スクリプス リサーチ インスティテュート | 細胞の再プログラム |
| EP4438734A2 (en) | 2010-06-14 | 2024-10-02 | The Scripps Research Institute | Reprogramming of cells to a new fate |
| AU2011267849B2 (en) * | 2010-06-15 | 2015-02-05 | FUJIFILM Cellular Dynamics, Inc. | Generation of induced pluripotent stem cells from small volumes of peripheral blood |
| JP5794588B2 (ja) | 2010-09-14 | 2015-10-14 | 国立大学法人京都大学 | 効率的な人工多能性幹細胞の樹立方法 |
| JP5921558B2 (ja) * | 2010-10-14 | 2016-05-24 | ユニバーシティ オブ セントラル フロリダ リサーチ ファウンデーション，インコーポレイテッド | 心臓人工多能性幹細胞ならびに心筋の修復および再生に使用する方法 |
| JP6182456B2 (ja) | 2010-12-22 | 2017-08-23 | フェイト セラピューティクス，インコーポレイテッド | 単細胞選別のための細胞培養プラットホームおよびｉＰＳＣの再プログラミングの増強 |
| CN103649112B (zh) | 2011-04-08 | 2017-07-18 | 国立大学法人大阪大学 | 改造层粘连蛋白及其利用 |
| CN103562376B (zh) * | 2011-04-08 | 2017-12-29 | 国家医疗保健研究所 | 复壮细胞的方法 |
| US10865383B2 (en) | 2011-07-12 | 2020-12-15 | Lineage Cell Therapeutics, Inc. | Methods and formulations for orthopedic cell therapy |
| WO2013022022A1 (ja) * | 2011-08-08 | 2013-02-14 | 国立大学法人京都大学 | 効率的な人工多能性幹細胞の樹立方法 |
| WO2013074916A1 (en) | 2011-11-18 | 2013-05-23 | Board Of Regents, The University Of Texas System | Car+ t cells genetically modified to eliminate expression of t- cell receptor and/or hla |
| US20130157368A1 (en) * | 2011-12-20 | 2013-06-20 | Advanced Technologies And Regenerative Medicine, Llc | Induced pluripotent stem cells prepared from human kidney-derived cells |
| US20130157365A1 (en) * | 2011-12-20 | 2013-06-20 | Advanced Technologies And Regenerative Medicine, Llc | Induced pluripotent stem cells from human umbilical cord tissue-derived cells |
| US10119150B2 (en) * | 2012-05-13 | 2018-11-06 | Allele Biotechnology & Pharmaceuticals, Inc. | Feeder-free Derivation of human-induced pluripotent stem cells with synthetic messenger RNA |
| US10155929B2 (en) * | 2012-05-13 | 2018-12-18 | Allele Biotechnology & Pharmaceuticals, Inc. | Feeder-free derivation of human-induced pluripotent stem cells with synthetic messenger RNA |
| WO2013176233A1 (ja) | 2012-05-23 | 2013-11-28 | 国立大学法人京都大学 | 効率的な人工多能性幹細胞の樹立方法 |
| CN102965393B (zh) * | 2012-11-06 | 2015-08-26 | 上海交通大学 | 人诱导多能干细胞的制备方法及其用途 |
| EP3323884A1 (en) | 2013-02-01 | 2018-05-23 | The United States Of America as Represented by the Secretary, Department of Health an Human Service | Method for generating retinal pigment epithelium (rpe) cells from induced pluripotent stem cells (ipscs) |
| WO2014192312A1 (ja) * | 2013-05-31 | 2014-12-04 | 国立大学法人 東京医科歯科大学 | 正常な内向きのカリウム電流特性を有するｉＰＳ細胞由来心筋モデル細胞 |
| WO2015006725A2 (en) | 2013-07-12 | 2015-01-15 | Cedars-Sinai Medical Center | Generation of induced pluripotent stem cells from normal human mammary epithelial cells |
| CN103571794B (zh) * | 2013-07-19 | 2016-01-20 | 中国医学科学院血液病医院（血液学研究所） | 一种抑制PUMA功能改善iPS细胞建立功效的方法 |
| CN103725710B (zh) * | 2013-12-25 | 2015-10-28 | 北京济福霖生物技术有限公司 | 一种可自我删除游离载体及其应用 |
| CN103740756B (zh) * | 2013-12-25 | 2015-08-05 | 中国农业大学 | 一种可调控删除的非病毒游离载体及其构建方法 |
| CN103740757B (zh) * | 2014-01-21 | 2016-04-20 | 中国科学院生物物理研究所 | 一种利用重编程制备猪神经干细胞的方法 |
| CN104830906B (zh) * | 2014-02-12 | 2018-09-04 | 北京维通达生物技术有限公司 | 一种重编程获得功能性人肝脏实质细胞的方法 |
| KR20240091064A (ko) | 2014-03-04 | 2024-06-21 | 페이트 세러퓨틱스, 인코포레이티드 | 개선된 재프로그래밍 방법 및 세포 배양 플랫폼 |
| US10233454B2 (en) | 2014-04-09 | 2019-03-19 | Dna2.0, Inc. | DNA vectors, transposons and transposases for eukaryotic genome modification |
| WO2015164740A1 (en) * | 2014-04-24 | 2015-10-29 | Board Of Regents, The University Of Texas System | Application of induced pluripotent stem cells to generate adoptive cell therapy products |
| EP3786285A1 (en) * | 2014-06-05 | 2021-03-03 | Cedars-Sinai Medical Center | A novel and efficient method for reprogramming immortalized lymphoblastoid cell lines to induced pluripotent stem cells |
| WO2016117139A1 (ja) * | 2015-01-20 | 2016-07-28 | タカラバイオ株式会社 | 神経系細胞の製造方法 |
| EP3250679B1 (en) * | 2015-01-30 | 2020-08-19 | Centre National de la Recherche Scientifique (CNRS) | Reprogramming method for producing induced pluripotent stem cells (ipsc) |
| CA2981715A1 (en) | 2015-04-06 | 2016-10-13 | The Board Of Trustees Of The Leland Stanford Junior University | Chemically modified guide rnas for crispr/cas-mediated gene regulation |
| EP3332020B1 (en) * | 2015-08-07 | 2023-12-20 | The J. David Gladstone Institutes, A Testamentary Trust Established under The Will of J. David Gladstone | Method of determining cellular protein homeostasis |
| AU2016321170B2 (en) | 2015-09-08 | 2022-09-01 | Fujifilm Cellular Dynamics | Method for reproducible differentiation of clinical-grade retinal pigment epithelium cells |
| AU2016318774B2 (en) | 2015-09-08 | 2022-08-18 | FUJIFILM Cellular Dynamics, Inc. | MACS-based purification of stem cell-derived retinal pigment epithelium |
| HUE056009T2 (hu) | 2015-10-08 | 2022-01-28 | Dna Twopointo Inc | DNS vektorok, transzpozonok és transzpozázok eukarióta genom módosítására |
| CN117737124A (zh) | 2015-10-16 | 2024-03-22 | 菲特治疗公司 | 用于诱导和维护基态多能性的平台 |
| US10865381B2 (en) | 2015-10-20 | 2020-12-15 | FUJIFILM Cellular Dynamics, Inc. | Multi-lineage hematopoietic precursor cell production by genetic programming |
| WO2017183736A1 (ja) | 2016-04-22 | 2017-10-26 | 国立大学法人京都大学 | ドーパミン産生神経前駆細胞の製造方法 |
| ES2904882T3 (es) * | 2016-04-29 | 2022-04-06 | Virogin Biotech Canada Ltd | Vectores de HSV con replicación mejorada en células cancerosas |
| GB201608944D0 (en) * | 2016-05-20 | 2016-07-06 | Ospedale San Raffaele And Fond Telethon | Gene Tharapy |
| US10221395B2 (en) | 2016-06-16 | 2019-03-05 | Cedars-Sinai Medical Center | Efficient method for reprogramming blood to induced pluripotent stem cells |
| US11572545B2 (en) | 2016-06-16 | 2023-02-07 | Cedars-Sinai Medical Center | Efficient method for reprogramming blood to induced pluripotent stem cells |
| AU2017290805B2 (en) | 2016-07-01 | 2023-11-16 | Research Development Foundation | Elimination of proliferating cells from stem cell-derived grafts |
| EP3491134B1 (en) | 2016-08-01 | 2023-10-11 | University of Pittsburgh - of The Commonwealth System of Higher Education | Human induced pluripotent stem cells for high efficiency genetic engineering |
| WO2018049168A1 (en) | 2016-09-09 | 2018-03-15 | The Board Of Trustees Of The Leland Stanford Junior University | High-throughput precision genome editing |
| US10961505B2 (en) | 2016-10-05 | 2021-03-30 | FUJIFILM Cellular Dynamics, Inc. | Generating mature lineages from induced pluripotent stem cells with MECP2 disruption |
| WO2018067836A1 (en) * | 2016-10-05 | 2018-04-12 | Cellular Dynamics International, Inc. | Methods for directed differentiation of pluripotent stem cells to hla homozygous immune cells |
| US11458225B2 (en) | 2016-11-09 | 2022-10-04 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | 3D vascularized human ocular tissue for cell therapy and drug discovery |
| US20190352670A1 (en) * | 2017-02-01 | 2019-11-21 | President And Fellows Of Harvard College | Methods for Increasing Efficiency of Gene Editing in Cells |
| CN106939299B (zh) * | 2017-02-04 | 2022-11-15 | 滨州医学院 | microRNA重编程体细胞为神经干细胞的制备方法及应用 |
| AU2018220843B2 (en) | 2017-02-14 | 2023-09-21 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Methods of engineering human induced pluripotent stem cells to produce liver tissue |
| DK3612557T3 (da) | 2017-04-18 | 2022-04-19 | Fujifilm Cellular Dynamics Inc | Antigenspecifikke immuneffektorceller |
| US11572544B2 (en) | 2017-06-14 | 2023-02-07 | The Children's Medical Center Corporation | Hematopoietic stem and progenitor cells derived from hemogenic endothelial cells by episomal plasmid gene transfer |
| EP3781675A1 (en) | 2018-04-20 | 2021-02-24 | FUJIFILM Cellular Dynamics, Inc. | Method for differentiation of ocular cells and use thereof |
| CN117982733A (zh) | 2018-11-19 | 2024-05-07 | 美国政府(由卫生和人类服务部的部长所代表) | 可生物降解的组织置换植入物及其用途 |
| EA202191463A1 (ru) | 2018-11-28 | 2021-10-13 | Борд Оф Риджентс, Дзе Юниверсити Оф Техас Систем | Мультиплексное редактирование генома иммунных клеток для повышения функциональности и устойчивости к подавляющей среде |
| CA3121210A1 (en) | 2018-11-29 | 2020-06-04 | Board Of Regents, The University Of Texas System | Methods for ex vivo expansion of natural killer cells and use thereof |
| CN109679918A (zh) * | 2018-12-25 | 2019-04-26 | 合肥中科干细胞再生医学有限公司 | 一种便捷的人诱导性多能干细胞的制备方法 |
| CN109666650A (zh) * | 2019-01-04 | 2019-04-23 | 北京航空航天大学 | 一种细胞重编程方法 |
| CN109913494A (zh) * | 2019-02-12 | 2019-06-21 | 北京呈诺医学科技有限公司 | 一种新的ips细胞的诱导方法 |
| CA3165346A1 (en) | 2020-01-23 | 2021-07-29 | George Q. Daley | Stroma-free t cell differentiation from human pluripotent stem cells |
| WO2021149824A1 (ja) * | 2020-01-24 | 2021-07-29 | アイ ピース， インコーポレイテッド | 人工多能性幹細胞の作製方法 |
| AU2021280343A1 (en) | 2020-05-29 | 2022-12-08 | FUJIFILM Cellular Dynamics, Inc. | Retinal pigmented epithelium and photoreceptor dual cell aggregates and methods of use thereof |
| JP2023536210A (ja) | 2020-05-29 | 2023-08-24 | フジフィルム セルラー ダイナミクス，インコーポレイテッド | 網膜色素上皮及び光受容体の二重層、並びにその使用 |
| WO2022019832A1 (en) * | 2020-07-20 | 2022-01-27 | Cellresearch Corporation Pte Ltd | A method of generating an induced pluripotent stem cell, an induced pluripotent stem cell and methods of using the induced pluripotent stem cell |
| CN114149974A (zh) * | 2020-09-08 | 2022-03-08 | 是光隽恒(北京)生物科技有限公司 | 诱导间充质干细胞成为多能干细胞的方法 |
| WO2022104109A1 (en) | 2020-11-13 | 2022-05-19 | Catamaran Bio, Inc. | Genetically modified natural killer cells and methods of use thereof |
| US20220162288A1 (en) | 2020-11-25 | 2022-05-26 | Catamaran Bio, Inc. | Cellular therapeutics engineered with signal modulators and methods of use thereof |
| GB202101107D0 (en) * | 2021-01-27 | 2021-03-10 | Oxford Genetics Ltd | Method of genome editing |
| US20220389436A1 (en) | 2021-05-26 | 2022-12-08 | FUJIFILM Cellular Dynamics, Inc. | Methods to prevent rapid silencing of genes in pluripotent stem cells |
| EP4347795A1 (en) | 2021-05-28 | 2024-04-10 | The United States of America, as represented by The Secretary, Department of Health and Human Services | Methods to generate macular, central and peripheral retinal pigment epithelial cells |
| AU2022282379A1 (en) | 2021-05-28 | 2023-11-30 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Biodegradable tissue scaffold with secondary matrix to host weakly adherent cells |
| KR20240055811A (ko) | 2021-09-10 | 2024-04-29 | 애질런트 테크놀로지스, 인크. | 프라임 편집을 위한 화학적 변형을 갖는 가이드 rna |
| US20230078230A1 (en) | 2021-09-13 | 2023-03-16 | FUJIFILM Cellular Dynamics, Inc. | Methods for the production of committed cardiac progenitor cells |
| CN113862221B (zh) * | 2021-10-27 | 2024-04-30 | 上海爱萨尔生物科技有限公司 | 外周血单个核细胞的培养液及培养方法 |
| US20240003871A1 (en) | 2022-06-29 | 2024-01-04 | FUJIFILM Cellular Dynamics, Inc. | Ipsc-derived astrocytes and methods of use thereof |
| CN115044590B (zh) * | 2022-06-30 | 2023-08-15 | 昆明理工大学 | p53基因突变体及其表达的蛋白在制备诊断和治疗肥厚型心肌病的药物中的应用 |
| US20240139256A1 (en) | 2022-09-30 | 2024-05-02 | FUJIFILM Cellular Dynamics, Inc. | Methods for the production of cardiac fibroblasts |
| WO2024192329A1 (en) | 2023-03-16 | 2024-09-19 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Methods for producing stable human chondroctyes and their use for promoting cartillage growth and repair |
Family Cites Families (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4937190A (en) | 1987-10-15 | 1990-06-26 | Wisconsin Alumni Research Foundation | Translation enhancer |
| DE60037394T2 (de) | 1999-01-29 | 2009-01-02 | The Board Of Trustees For The University Of Illinois, Urbana | VERWENDUNG VON p53 INHIBITOREN ZUR BEHANDLUNG VON NEBENERSCHEINUNGEN BEI DER KREBSTHERAPIE |
| ATE367445T1 (de) | 1999-05-18 | 2007-08-15 | Dnavec Research Inc | Viraler paramyxoviridae vektor mit einem defekten hüllprotein-gen |
| JP2008528038A (ja) | 2005-01-31 | 2008-07-31 | エス セル インターナショナル ピーティーイー リミテッド | 胚性幹細胞の指示された分化及びその利用 |
| US8278104B2 (en) * | 2005-12-13 | 2012-10-02 | Kyoto University | Induced pluripotent stem cells produced with Oct3/4, Klf4 and Sox2 |
| EP3418297B1 (en) | 2005-12-13 | 2023-04-05 | Kyoto University | Nuclear reprogramming factor |
| WO2007080590A2 (en) | 2006-01-11 | 2007-07-19 | Technion Research & Development Foundation Ltd. | Human embryonic stem cell-derived connective tissue progenitors for tissue engineering |
| CA2684242C (en) | 2007-03-23 | 2019-11-12 | Wisconsin Alumni Research Foundation | Somatic cell reprogramming |
| WO2008144580A2 (en) | 2007-05-17 | 2008-11-27 | Oregon Health & Science University | Primate stem cells produced by somatic cell nuclear transfer |
| CA2660123C (en) * | 2007-10-31 | 2017-05-09 | Kyoto University | Nuclear reprogramming method |
| AU2008286249B2 (en) | 2007-12-10 | 2013-10-10 | Kyoto University | Efficient method for nuclear reprogramming |
| WO2009115295A1 (en) * | 2008-03-17 | 2009-09-24 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) | Vectors and methods for generating vector-free induced pluripotent stem (ips) cells using site-specific recombination |
| CN101550406B (zh) | 2008-04-03 | 2016-02-10 | 北京大学 | 制备多潜能干细胞的方法,试剂盒及用途 |
| JP2011522540A (ja) | 2008-06-04 | 2011-08-04 | セルラー ダイナミクス インターナショナル， インコーポレイテッド | 非ウイルスアプローチを用いたｉＰＳ細胞の産生のための方法 |
| EP2300611B1 (en) * | 2008-06-13 | 2017-08-09 | Whitehead Institute for Biomedical Research | Programming and reprogramming of cells |
| JP5340265B2 (ja) * | 2008-06-27 | 2013-11-13 | 国立大学法人京都大学 | 効率的な人工多能性幹細胞の樹立方法 |
| EP2307539B1 (en) | 2008-07-30 | 2014-11-19 | Kyoto University | Method of efficiently establishing induced pluripotent stem cells |
| AU2008360135A1 (en) | 2008-07-31 | 2010-02-04 | Gifu University | Efficient method for establishing induced pluripotent stem cells |
| US20110003365A1 (en) | 2009-05-29 | 2011-01-06 | Kyoto University | Method of preparing induced pluripotent stem cells deprived of reprogramming gene |
| WO2011016588A1 (en) | 2009-08-07 | 2011-02-10 | Kyoto University | Method of efficiently establishing induced pluripotent stem cells |
| CN102803476A (zh) | 2009-09-14 | 2012-11-28 | 程临钊 | 血细胞重编程产生多潜能干细胞和多功能干细胞 |
| EP2536828B1 (en) | 2010-02-16 | 2015-09-09 | Kyoto University | Method of efficiently establishing induced pluripotent stem cells |
| WO2011119942A1 (en) | 2010-03-25 | 2011-09-29 | Vistagen Therapeutics, Inc. | Induction of ips cells using transient episomal vectors |
| US8765470B2 (en) | 2010-08-04 | 2014-07-01 | Cellular Dynamics International, Inc. | Reprogramming immortalized B-cells to induced pluripotent stem cells |
| WO2013022022A1 (ja) | 2011-08-08 | 2013-02-14 | 国立大学法人京都大学 | 効率的な人工多能性幹細胞の樹立方法 |
| WO2013176233A1 (ja) | 2012-05-23 | 2013-11-28 | 国立大学法人京都大学 | 効率的な人工多能性幹細胞の樹立方法 |
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| EP2462225B1 (en) | 2019-03-06 |
| EP2462225A1 (en) | 2012-06-13 |
| CN102625837B (zh) | 2015-01-14 |
| ES2726766T3 (es) | 2019-10-09 |
| CA2770412C (en) | 2018-09-11 |
| EP2462225A4 (en) | 2013-12-18 |
| SG178197A1 (en) | 2012-03-29 |
| KR101774206B1 (ko) | 2017-09-04 |
| CN102625837A (zh) | 2012-08-01 |
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